<p>WD Repeat Domain 5 Promotes Invasion, Metastasis and Tumor Growth in Glioma Through Up-Regulated Zinc Finger E-Box Binding Homeobox 1 Expression</p>

Abstract

Background: Glioma is one of the important diseases that threaten human survival in today's society. WD repeat domain 5 (WDR5) belongs to the components of the lysine methyltransferase complex. WDR5 is involved in gene transcription regulation, cell senescence, cancer and other biological events through methylation modification. However, its expression and function in glioma are still unclear. Materials and Methods: The expression of WDR5 was observed in glioma cells, and then a glioma cell line SW1783 knocked down WDR5 was established. The effects of the decrease of WDR5 expression on proliferation, migration, invasion and EMT of glioma cells were detected, respectively. The downstream regulators of WDR5 were identified by gene expression profiling technology, and the possible molecular mechanisms were identified. Results: In this study, we found that WDR5 could promote glioma cell's proliferation, migration, invasion and tumor metastasis. In glioma, especially in metastatic glioma tissues, WDR5 levels were significantly increased, the higher expression level could also cause a significant reduction in overall survival of glioma patients. Second, the ability of cells' proliferation, migration, invasion and tumor metastasis was significantly reduced in WDR5 knockdown cell lines. We also found a significant change in the expression level of epithelial and mesenchymal markers in WDR5 knockdown cell lines. Furthermore, we found that knockdown of WDR5 could inhibit the expression of zinc finger E-box binding homeobox 1 (ZEB1), and knockdown of ZEB1 could inhibit invasion, migration and epithelial-mesenchymal transformation (EMT) in WDR5 over-expression cell line. We also found that WDR5 may regulate ZEB1's expression through H3K4me3. Conclusion:In summary, in this study, we have studied the relationship between WDR5 and glioma, and found that WDR5's expression is positively correlated with the proliferation, migration, and invasion of glioma cells, which will help find the potential therapeutic target for glioma patients.

WDR5 facilitates EMT and metastasis of CCA by increasing HIF-1α accumulation in Myc-dependent and independent pathways

“…The correlation between WDR5 and metastasis has been hinted at in breast cancer, glioma, and colon cancer, by participating in several signaling pathways such as transforming growth factor (TGF)-b signaling and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. 16,56,57 For the first time, we linked WDR5 with HIF-1a and its downstream TWIST1 and suggested that WDR5 resulted in metastasis by promoting HIF-1a-induced EMT. This conclusion enhanced current understanding of WDR5 as an oncoprotein, especially in CCA.…”

WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma

“…Previous studies demonstrated that WDR5 mediates self-renewal in embryonic stem cells by regulating the OCT4-SOX2-NANOG pluripotency transcription factor network (Ang et al, 2011). While WDR5 has been documented to be expressed in GBM and neuroblastoma and functionally important in high-passage GBM models (Dai et al, 2020; Wang et al, 2020), WDR5 function has not been investigated in the cancer stem cell state in GBM or in GBM organoid culture, and therapeutic inhibition of WDR5 has not been tested in GBM.…”

“…While WDR5 has been documented to be expressed in GBM and neuroblastoma and functionally important in high-passage GBM models (Dai et al, 2020;Wang et al, 2020), WDR5 function has not been investigated in the cancer stem cell state in GBM or in GBM organoid culture, and therapeutic inhibition of WDR5 has not been tested in GBM.…”

USP44 accelerates the growth of T-cell acute lymphoblastic leukemia through interacting with WDR5 and repressing its ubiquitination

“…Besides, USP44 and WDR5 are also associated with the metastasis of cancer, such as the migration and invasion capability of cancer cells and vasculogenic mimicry [12,13,27,[36][37][38]. WDR5 is also related to the liver infiltration of leukemia cells [23].…”